Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia.
Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia.
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t(8;21) 白血病中 AML1/RUNX1 和 ETO 中的基因组 DNA 断点与拓扑异构酶 II DNA 切割和 DNase I 超敏位点簇。
DOI：
10.1073/pnas.042702899
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发表时间：
2002
影响因子：
11.1
通讯作者：
Rowley,JanetD
中科院分区：
文献类型：
--
作者：
Zhang,Yanming;Strissel,Pamela;Strick,Reiner;Chen,Jianjun;Nucifora,Giuseppina;LeBeau,MichelleM;Larson,RichardA;Rowley,JanetD
易位t（8; 21）（q22; q22）是急性髓系白血病（AML）中最常见的染色体易位之一。21 q22处的AML 1/RUNX 1参与了t（8;21）、t（3;21）和t（16;21）的新发和治疗相关的AML和骨髓增生异常综合征，以及儿童B细胞急性淋巴细胞白血病的t（12;21）。虽然AML 1和ETO的DNA断裂点（在8 q22）聚集在少数内含子中，但导致t（8;21）的DNA重组机制尚不清楚。特定染色质结构元件的相关性，即，拓扑异构酶II（topo II）DNA切割位点、DNase I超敏位点和支架相关区域，这些区域与AML 1和ETO in t（8;21）中的基因组DNA断裂点的染色体重组有关，目前尚不清楚。AML 1和ETO的断裂点在Kasumi 1细胞系和31例t（8;21）白血病患者中聚集;除1例外，所有患者均为初发AML。在AML 1中定位了Tenin vivotopo II的DNA切割位点，其中3个位于ETO的内含子5，7个位于内含子7a，2个位于内含子1b。所有强拓扑异构酶II位点与DNA酶I超敏感位点共定位，因此代表开放的染色质区域。这些位点与AML 1和ETO的基因组DNA断裂点相关，从而暗示它们与de novo 8;21易位有关。
The translocation t(8;21)(q22;q22) is one of the most frequent chromosome translocations in acute myeloid leukemia (AML).AML1/RUNX1at 21q22 is involved in t(8;21), t(3;21), and t(16;21) inde novoand therapy-related AML and myelodysplastic syndrome as well as in t(12;21) in childhood B cell acute lymphoblastic leukemia. Although DNA breakpoints inAML1andETO(at 8q22) cluster in a few introns, the mechanisms of DNA recombination resulting in t(8;21) are unknown. The correlation of specific chromatin structural elements, i.e., topoisomerase II (topo II) DNA cleavage sites, DNase I hypersensitive sites, and scaffold-associated regions, which have been implicated in chromosome recombination with genomic DNA breakpoints inAML1andETOin t(8;21) is unknown. The breakpoints inAML1andETOwere clustered in the Kasumi 1 cell line and in 31 leukemia patients with t(8;21); all except one hadde novoAML. Sequencing of the breakpoint junctions revealed no common DNA motif; however, deletions, duplications, microhomologies, and nontemplate DNA were found. Tenin vivotopo II DNA cleavage sites were mapped inAML1, including three in intron 5 and seven in intron 7a, and two were in intron 1b ofETO. All strong topo II sites colocalized with DNase I hypersensitive sites and thus represent open chromatin regions. These sites correlated with genomic DNA breakpoints in bothAML1andETO, thus implicating them in thede novo8;21 translocation.